When "personalized gene-targeted cancer therapy" really means "making it up as you go along"

Last week, I applied a little not-so-Respectful Insolence to a movie about a physician and "researcher" named Stanislaw Burzynski, MD, PhD, founder of the Burzynski Clinic and Burzynski Research Institute in Houston. I refer you to my original smackdown for details, but in brief Dr. Burzynski claimed in the 1970s to have made a major breakthrough in cancer therapy through his discovery of anticancer substances in the urine that he dubbed "antineoplastons," which turned out to be mainly modified amino acids and peptides. Since the late 1970s, when he founded his clinic, Dr. Burzynski has been using antineoplastons to treat cancer. Over the last 25 years or so, he has opened a large number of phase I and phase II clinical trials with little or nothing to show for it in terms of convincing evidence of efficacy. Worse, as has been noted in a number of places, high doses of antineoplastons as sodium salts are required, doses so high that severe hypernatremia is a concern.

Although antineoplastons are the dubious cancer therapy upon which Dr. Burzynski built his fame, they aren't the only thing he does. Despite the promotion of the Burzynski Clinic by natural medicine mavens as using "nontoxic" therapies that "aren't chemotherapy," Dr. Burzynski's dirty little secrets, at least as far as the "alternative medicine" crowd goes, are that (1) despite all of the attempts of Dr. Burzynski and supporters to portray them otherwise antineoplastons are chemotherapy and (2) Dr. Burzynski uses a lot of conventional chemotherapy. In fact, from my perspective, it appears to me as though over the last few years Dr. Burzynski has pivoted. No longer are antineoplastons the center of attention at his clinic. Rather, these days, he appears to be selling something that he calls "personalized gene-targeted cancer therapy." But what is "personalized gene-targeted cancer therapy," according to Dr. Burzynski? Here is how it is described:

Our approach to cancer is a result of Dr. Burzynski's extensive experience in cancer research in the field of genetics and genomics.

Personalized Treatments offered by the Burzynski Clinic are individual treatment plans, customized for each patient, based on:

Identification of oncogenes responsible for the growth of cancerous cells in individual patients

In some cases conventional therapy is the most appropriate treatment for a patient. Our Clinic offers customized combination therapies consisting of conventional therapy and other approved targeted therapies to maximize effectiveness while minimizing the side effects that typically occur when using the traditional therapies alone.

And:

There are currently close to 30 targeted therapeutics approved by the FDA (as of January 2011). This number grows rapidly with the advancement of the research in genomics. All of the Food and Drug Administration (FDA)-approved gene-targeted medications are available for treatment at the Burzynski Clinic. The combination of targeted medications is customized for each patient and determined by the type of oncogenes involved in patient's cancer (Personalized Treatment).

Dr. Burzynski is also not shy about being interviewed by promoters of alternative medicine, such as Mike Adams. For example, here are a typical radio interview (on Oprah Radio, of course!) and videos like this one:

Note that the first few minutes of the second video are spent portraying Dr. Burzynski as the prototypical "brave maverick doctor," a misunderstood genius, a pioneer being oppressed, suppressed, and persecuted by The Man. Dr. Burzynski also calls the FDA and NCI "criminal" and uses every "health freedom" argument in the book, while his antineoplastons are portrayed as a cancer cure that causes brain tumors to "vanish in many children." Finally, around the 4:30 mark, we see Dr. Gregory Burzynski, Dr. Burzynski's son, talking about genomic profiling of cancers and biomarkers in the blood and in circulating tumor cells. If this segment weren't embedded in a bunch of paranoid conspiracy mongering about big pharma, the FDA, and the NCI, plus a claim that surgery will no longer be necessary for surgery, what's left over doesn't sound too different from what quite a few "conventional" cancer researchers say about "personalized medicine." Well, that and what Dr. Burzynski says about tumor suppressors. He seems to think that all tumor suppressors prevent mutations, which is, of course, not true. Some of them do other things. Be that as it may, the claim made in the video is that, with a combination of antineoplastons and "personalized therapy," Dr. Burzynski can cure many cancer patients with stage IV disease. But how credible is this claim? What, exactly, is he doing? It's hard to figure out from his website, but looking elsewhere can provide hints. Let's

"Personalized cancer treatment" in science-based medicine

At the risk of annoying some colleagues I know, I'm going to point out that I never really liked the term "personalized cancer therapy" or its many variants, for the simple reason that it always struck me as more of a marketing term than a scientifically meaningful description of what targeting therapy to the genetic makeup of a patient's tumor will eventually entail. In fact, I think I now prefer another term, which has been used by Cancer Research U.K., namely "stratified medicine." The reason is that what we as clinicians are doing when we "personalize" or "individualize" therapies isn't really "personalizing" the therapy so much as using various measurements and biomarkers to place patients into groups of patients who respond to specific therapies. What the modern version of "personalized" therapy is really doing is producing more and more groups of patients, each of which, is smaller than the last, to be matched to more and more therapies. Whether the groups will eventually reach an N of 1, I don't know, but that is the goal. Only then will we truly have "personalized medicine."

My personal irritation at the proliferation of certain terms notwithstanding, I actually do believe that the stratification and matching of patients with therapies based on genomics, proteomics, and biomarkers is the future of cancer treatment, and, to some extent, the future is now. However, "personalized" medicine is in its infancy, as I have pointed out in previous posts on the topic, Progress mixed with hype in genomics and "personalized medicine" and Integrating patient experience into research and clinical medicine: Will this lead to true "personalized medicine"? True, we do have several targeted therapies that inhibit or target a single important molecule. For instance, in breast cancer, Herceptin (trastuzumab) targets the HER2 oncogene, which is amplified in some breast cancers. Another example, Gleevec (imatinib mesylate), inhibits the tyrosine kinase activity of the bcr-abl oncogene product as well as receptor tyrosine kinases encoded by the c-kit and platelet-derived growth factor receptor oncogenes and is very effective against tumors that make too much of one these oncogenes, such as gastrointestinal stromal tumor and Philadelphia-positive (Ph+) hematological malignancies such as chronic myelogenous leukemia and acute lymphoblastic leukemia. Now, there are numerous other examples, so many that they are listed on the NCI website.

In fact, the idea of targeted therapy in cancer is not new. For example, it's long been known that the presence of the estrogen receptor (ER) in breast cancer implies that treatment with antiestrogen drugs like Tamoxifen is likely to result in a a response and that lack of ER in a tumor means that Tamoxifen won't work. Similarly, we've used prostate-specific antigen (PSA) as a biomarker for prostate cancer and carcinoembryonic antigen (CEA) as a biomarker for colon cancer for decades. The difference between the way drugs were targeted to cancers a couple of decades ago and now is the explosion of genomics knowledge that has occurred over the last decade. As I've pointed out, we are now producing terrabytes and petabytes of genomic data about cancers, a flood of information that we have only relatively recently started seriously developing the tools needed to analyze this flood of data and disciplines (systems biology, bioinformatics, genomics, etc.) to organize and determine how best to translate it into therapies. We even use one such test in breast cancer, the Oncotype DX, assay, which has allowed oncologists to identify patients who can safely skip adjuvant chemotherapy.

What we are learning, as I have lightheartedly appropriated a quote from Douglas Adams' masterwork to say before, is that cancer is complicated. You just won't believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think it's complicated to understand basic cell biology, but that's just peanuts to cancer. All you have to do is to look at the genetic derangements in typical prostate cancers to get a flavor for how daunting the task of developing personalized treatments of cancer will be, much less curing it. Think of it this way. The examples of genomic derangements in a few prostate cancers were incredible, and there are different sets of genomic derangements that vary by cancer type, of which there are hundreds. Add to that the fact that, as Dr. Burzynski himself emphasizes, cancers are heterogeneous, with different genetic derangements in different parts of the tumor, and you get a flavor of how difficult "personalizing" cancer therapy based on its genomic makeup and biomarkers will be. It will take an incredible amount of research, both basic and clinical, in order to learn the best ways to match the genomic makeup of patient tumors to the most effective targeted therapies.

Unfortunately, Burzynski's approach to "personalized gene-targeted anticancer therapy" appears to fall prey to the assumption that he knows enough about the molecular pathways to be investigated to reliably use the results of various genomics assays to guide anticancer treatment. In essence, it's as though Dr. Burzynski read a book called Personalized Cancer Therapy for Dummies and decided he is an expert in genomics-based tailoring of targeted therapies to individual cancer patients. I'll try to show you what I mean.

What Burzysnki claims he can do with "personalized gene-targeted therapy"

What interested me about this video, ironically enough, is how bland and unremarkable a lot of it was. Clearly, the producer went to great lengths to make Burzynski's lab look like any other molecular and cell biology lab--even like my lab. The other thing that interested me was how the video emphasizes the use of FDA-approved medications. Finally, there was a clue (to me, at least) about what it is that Burzynski is doing. At around the three minute mark, the announcer states:

We combine gene-targeting drugs and low dose chemo, if needed.

Then a very sharply-dressed man named Azad Rastegar appears and says:

The way we look at cancer here at the Burzynski Clinic is that it's more than just the tumor site. Obviously, that's very important and significant for figuring out how to address the cancer in the patient, but what we want to do is to identify the genes that are involved in that particular patient's cancer. With that, then we can start creating more customized and personalized treatment plans that involve gene-targeted medications targeting, obviously, the genes involved in that patient's cancer. This way we're able to reduce side effects. We're able to reduce any time-wasting on ineffective drugs and cater it, obviously, much more to the patients and their individual cancer needs.

It all sounds so reasonable, and, indeed, this is exactly the sort of thing that lots of cancer centers are trying to do. But how this sort of approach is implemented makes all the difference in the world, and the question I had was whether Dr. Burzynski is taking anything resembling the right sort of approach to this problem. From the description above, it sounded very much to me as though Dr. Burzynski is combining various targeted agents with metronomic chemotherapy. I know a thing or two about metronomic chemotherapy, because I was involved in a project whose end result was to be the testing of metronomic chemotherapy against cancer and because the concept is a spinoff of the work of one of my scientific heros, the late Judah Folkman. Basically, metronomic chemotherapy is an approach to chemotherapy that uses repetitive, low doses of chemotherapy drugs (or even continuous infusions of low dose chemotherapy) designed to minimize toxicity and target the tumor blood vessels rather than targeting the tumor cells themselves. The concept behind this strategy is that blood vessels are lined by genetically stable endothelial cells, they do not evolve resistance, and chemotherapy can be antiangiogenic. The drawback to metronomic chemotherapy is that long periods of therapy may be required and the cumulative doses of chemotherapy may end up being actually higher than more standard therapies. On the other hand, this latter aspect may not be a drawback because metronomic chemotherapy may allow a greater cumulative dose, with a concurrent greater cumulative effect. Unfortunately, thus far clinical trials in humans of such approaches can only be characterized as fairly disappointing.

For the majority of Dr. Burzynski's patients he does not use any chemotherapy, but for some patinets the chemotherapy is used in lower dosages, which are below the threshold of significant side effects. Dr. Burzynski takes advantage of the synergistic effect of such combinations...

Except that he doesn't demonstrate that these combinations are synergistic in preclinical studies or clinical trials before prescribing them off-label.

SB: At the moment we use a different approach. We study which genes in individual patients are abnormal, trying to determine the genetic signature of cancer in these patients. With our methods, we can have answers for the patient in about three days based on blood tests. Once we identify the most important oncogenes involved in cancer for that individual, we select a group of four to six medications from those twenty-four which are now approved by the FDA and use them to hit those genes which are causing the cancer to progress. This is like "boutique treatment" because for every patient we design a treatment plan. When we do this we have a very good chance to have positive results in most patients.

SS: How many respond?

SB: About 85 per cent for whom we have the proper gene signature; about 15 percent do not respond. In our responders many of them have tumors which disappear completely and in others the tumors remain small. The problem is finding the genetic signature because for many of these different genetic signatures we don't have blood tests...yet.

Note that at the time this book was published, Dr. Burzynski was claiming that he could identify who would benefit from specific targeted therapies simply from blood tests. If he could do this for real, Burzynski could easily publish in high impact journals like Clinical Cancer Research, the Journal of Clinical Oncology, or another high impact clinical cancer journal. Heck, a result like that could probably make it into general medical journals, such as the New England Journal of Medicine or The Lancet, which have an even higher impact factor. If he were able to demonstrate that his method of testing tumors and picking targeted therapy could result in a complete response rate anywhere near 85% for breast cancer, even more so. If, as he claims later in the chapter, Dr. Burzynski has patients with pancreatic cancer and advanced liver cancer whose tumors have disappeared within two months after he began treatment, the same would be true. If, as Burzynski claims, he achieves a 50% complete response rate in advanced brain tumors, again, the same would be true. He doesn't submit his results to these journals. Why not? No doubt it's The Man keeping him down.

So what tests does Dr. Burzynski use to determine the cocktail of targeted therapies to use in any given patient, anyway?

Caris Life Sciences'â¢ molecular profiling test, Caris Target Nowâ¢, examines the genetic and molecular changes unique to a patient's tumor so that treatment options may be matched to the tumor's molecular profile.

Caris Target Now helps patients and their treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor's information with data from published clinical studies by thousands of the world's leading cancer researchers, Caris can help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

The Caris Target Now test is performed after a cancer diagnosis has been established and the patient has exhausted standard of care therapies or if questions in therapeutic management exist. Using tumor samples obtained from a biopsy, the tumor is examined to identify biomarkers that may have an influence on therapy. Using this information, Caris Target Now provides valuable information on the drugs that will be more likely to produce a positive response. Caris Target Now can be used with any solid cancer such as lung cancer, breast cancer, and prostate cancer.

It's also noted:

Caris Target Nowâ¢ was developed and its performance characteristics were determined by Caris Life Sciences, a medical laboratory CLIA-certified in compliance with the U.S. Clinical Laboratory Amendment Act of 1988 and all relevant U.S. state regulations. It has not been approved by the United States Food and Drug Administration.

All of which sounds suspiciously like a Quack Miranda Warning. At least, it's a little too close for comfort in my book. From my perspective, this test looks perfectly fine as a test to be used for research and clinical trials, but clearly using it to treat patients with off-label cancer drugs is something that I'd be very, very concerned about.

Caris Target Now begins with an immunohistochemistry (IHC) analysis. An IHC test measures the level of important proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run.

If there is access to a frozen sample of patient tissue available, Caris Life Sciencesâ¢ may also run a gene expression analysis by microarray. The microarray test looks for genes in the tumor that are associated with specific treatment options.

As deemed appropriate based on each patient, Caris will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the DNA tumor.

Immunohistochemistry is standard for many cancers. For example, in breast cancer, pretty much every pathology lab does immunohistochemistry (using antibodies to detect specific proteins) for at least two proteins, the estrogen receptor and the HER2 oncogene. Sometimes, depending upon the lab and the clinical situation, pathologists will stain for proliferation markers, like Ki-67, or other receptors such as epidermal growth factor receptor. Not uncommonly, pathologists stain for E-cadherin in order to differentiate between two common types of breast cancer, infiltrating ductal carcinoma versus lobular carcinoma. similarly, breast cancers are often subjected to FISH in order to determine whether the HER2 oncogene is amplified. In other words, none of this is anything particularly remarkable from a clinical standpoint.

What Caris appears to do that's different from normal clinical evaluation of a tumor sample is, if fresh frozen tissue is available, the performance of cDNA microarray analysis of the messenger RNA isolated from the tumor tissue. cDNA microarrays are a technology that allows scientists to analyze the level of messenger RNA from every known gene in the genome simultaneously. In actuality, technology has moved on from cDNA microarrays, which these days are so 2005, but they're still good tools and still used to examine differences of thousands of genes simultaneously, either between tissues or in response to drugs or other interventions. Also, newer technology, such as next generation sequencing (NGS) and RNA-Seq. RNA-Seq, for instance, provides the same information that a cDNA microarray does, plus everything else in the transcriptome, such as microRNAs and long non-coding RNAs. microRNAs, in particular, are being appreciated as very important regulators of gene activity because a single microRNA can often regulate hundreds of genes. RNA-Seq is also unbiased in that cDNA microarrays can only measure genes we know, whereas RNA-Seq can be used for discovery of previously unknown RNAs.

However, these techniques are expensive and not yet as common and practical as cDNA microarrays. That Caris isn't using the latest technology for the test doesn't mean it might not be potentially worthwhile; after all, a cDNA microarray will detect the levels of all known oncogenes. Caris also apparently does some mutational analysis and fluorescence in situ hybridization (FISH), a test designed to measure gene copy number and thus detect amplified genes. The result is a report like this example report that Caris Life Sciences has posted on one of its websites. The problem, of course, is what a clinician should do with the results. That's why I say that such a test should probably, except in rare circumstances, only be used for research purposes. Besides, much of what I see isn't that helpful anyway. For example, if you look at the report, the first agents listed are anthracyclines, such as doxorubicin, because topoisomerase-2A is elevated and taxanes, such as paclitaxel, because TLE3 is elevated. These are basically "Well, duh!" suggestions, because doxorubicin and paclitaxel are normally standard-of-care chemotherapeutic agents for triple negative breast cancer anyway! Particularly useless is the mention that "Lack of HER2 amplification has been associated with lack of benefit from HER2-targeted antibody." No kidding, given that trastuzumab was designed to treat HER2-positive breast cancer and that clinical samples are routinely checked for HER2 amplification as part of the standard-of-care!

As for the other recommendations, the gene associations listed, many of them are based on associations with response to specific therapies in other tumor types, such as irinotecan in ovarian cancer and cisplatin in gastric cancer, small cell lung cancer, for example. The relevance of many of these recommendations to breast cancer is questionable, to say the least. To apply them to individual patients outside the context of a clinical trial is hard to justify except in rare cases, but that's exactly what Dr. Burzynski appears to be doing for large numbers of his patientss, picking off-label chemotherapeutic agents based on the results of this test and selling it as "personalized gene-targeted therapy" without letting patients know that (1) the evidence base behind these recommendations is often not relevant to the specific tumors being treated because it's from different cancers; (2) the studies used to support these recommendations have a lot of uncertainty; and (3) most of these recommendations haven't been validated in clinical trials.

Even worse, the very concept of "gene-targeted cancer therapy" hasn't been convincingly shown to improve cancer outcomes, at least not yet. Believe it or not, I actually am in the camp who believes that eventually such a strategy will ultimately be proven useful and revolutionize cancer therapy, but that time is not yet. Gene-targeted cancer therapy is currently in its infancy and, except in rare situations outside of the existing currently validated biomarkers (such as HER2, ER, c-kit, and other genes for which targeted therapies exist) for the response of specific cancers, is not to be undertaken outside of the context of a clinical trial. In essence, Burzynski appears to be using such information on a "make it up as you go along" sort of fashion. Indeed, an e-mail from Renee Trimble confirmed this suspicion of mine when I pointed out to her that gene-targeted cancer therapy is in its infancy and that in the vast majority of cases we don't know what to do with this information. I also wanted to know what the Burzynski Clinic was doing that is different from what the major cancer centers are doing. Her answer was, to put it mildly, unsatisfying, as I will discuss in the next section.

Compare and contrast, ideal versus results

Before discussing how the Burzynski Clinic does personalized cancer therapy, I think it's worth looking at how real scientists do it right now. In essence, real scientists use information of the sort provided by Caris Life Sciences or by their own genomic testing to stratify patients and identify them for clinical trials. An excellent example of this is a study hot off the presses in the November issue of Science Translational Medicine by a group from my very own alma mater, the University of Michigan entitled Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study. In essence, the investigators (Roychowdhury et al) began a pilot study to study the practical difficulties involved in using high-throughput sequencing in clinical oncology, which they identified in the introduction:

Translating high-throughput sequencing for biomarker-driven clinical trials for personalized oncology presents unique logistical challenges, including (i) the identification of patients who could benefit, (ii) the development of an informed consent process that includes a way to deal with incidental findings, (iii) the implementation of efficient and integrative computational pipelines for data analysis, (iv) the selection of the results that should be disclosed to patients, and (v) the completion of the sequencing analysis in a cost-effective and clinically relevant time frame (Table 1). We implemented an exploratory study that we call the Michigan Oncology Sequencing Project (MI-ONCOSEQ) to address these challenges.

The challenges, and the response of investigators, are well described in Table I:

Before undertaking this study in actual humans, in order to verify that their sequencing strategy would work, Roychowdry et al first grew in mice xenografts made from tissue taken from the tumors of two patients with metastatic prostate cancer. They performed their genomic analysis and found that one carried a common gene fusion found in prostate cancer and another previously undescribed gene fusion. They also found the androgen receptor gene was amplified and two tumor suppressors were inactivated. For purposes of the study, they set up a special tumor board to evaluate their findings and decide what clinical trials would be best for a patient. The authors then tried their strategy on two actual patients, one with colorectal cancer and one with melanoma. The tumor board suggested a combination of inhibitors that would be suitable for each patient on clinical trial. Unfortunately, at the time there were no appropriate clinical trials. This is the sort of preliminary work that needs to be done before genomic analysis of individual patient tumors, as will the implementation of clinical trials that patients can be assigned to based on their genomic information.

Another example was reported this spring, when M.D. Anderson Cancer Center presented initial data at ASCO for over 1,000 patients in a phase I trial in which patients' tumors were analyzed for genetic abnormalities and, when a drug existed to target that genetic abnormality, received that drug. Unfortunately, I didn't go to ASCO this year; so I didn't see the presentation, but the results are summarized on the M.D. Anderson Cancerwise blog:

For the 175 patients with one aberration, the medical response rate was 27% with matched targeted therapy. The response rate was 5% in 116 patients when treated with non-matched therapy.

Patients who received matched targeted therapy had median survival of 13.4 months, compared to nine months for unmatched targeted therapy. Median survival without cancer progression was 5.2 months for those receiving matched therapy, compared to 2.2 months for patients who received unmatched therapy.

True, this is not a home run by any means, but it suggests that "personalized" cancer therapy can improve outcomes.

Now let's take a look at how the Burzynski Clinic does it, at least as far as I can figure out from my various sources and from Ms. Trimble. In response to my query about personalized gene-targeted therapy offered by the Burzynski Clinic, Ms. Trimble stated that a gene expression analysis is performed, as well as mutational analysis, FISH, immunohistochemistry for selected genes and that a blood test is also performed to measure the "concentration of proteins which are products of most important oncogenes." How on earth they do this latter test, I really don't know, because most oncogenes are not secreted proteins and most cancers don't have good serum biomarkers. Next, according to Ms. Trimble, the "medications which are shown to be best candidates for treatment, as well as those which are poor candidates, are identified from FDAs' approved gene targeted medications and chemotherapy drugs list." In addition, drugs are supposedly selected based on the patient's clinical information, standard of care, FDA indication, data from phase II and III clinical trials. On the surface, up to this point it all sounded reasonable and not unlike what is being done at quite a few big cancer centers, hence my question (which was never answered to my satisfaction) of what Burzynski is doing that is different from (and presumably believed by Burzynski to be superior to) what everyone else is doing.

Then there was a hint. In addition, Burzynski then formulates a preliminary treatment plan that "will consist of medications which should cover approximately between 100 to 200 genes," after sometimes doing a SNP analysis to "eliminate drugs which are not metabolized properly." The result, or so it is claimed, is a set of drugs that have "synergistic activity which permits reduction of doses." But why 100 to 200 genes? The very idea of targeted therapy is to hit the bare minimum of targets necessary to eradicate or control the tumor. Burzynski is going against the very concept of targeted therapy by making sure his therapy hits "100 genes," a claim that resonates from what he said in the movie about him I reviewed last week. According to Ms. Trimble, "Antineoplastons and their prodrug, phenyl butyrate, are important ingredients of the combination because they cover the spectrum of approximately 100 genes."

To support this claim, Ms. Trimble also sent me two papers from the Burzynski Clinic, both of which appeared in a journal I had never heard of before, the Journal of Cancer Therapy, which is clearly not indexed on PubMed because these papers never showed up when I searched PubMed for Burzynski. One described Burzynski's approach for triple negative breast cancer (TNBC), the other for esthesioneuroblastoma and nonsmall cell lung cancer. What I found odd about both of these papers is that neither of them really examined whole genome expression profiling, although the paper about triple negative breast cancer did mention measuring the expression of "important" oncogenes. Meanwhile, the paper on esthesioneuroblastoma and nonsmall cell lung cancer primarily used sodium phenylbutyrate rather than any sort of gene targeting. I note that, while the esthesioneuroblastoma case is mildly interesting, it is a case report. I also note that the TNBC paper is a case report and small series in which a cocktail of targeted therapies plus chemotherapy appear to have produced somewhat durable responses. Unfortunately, in the absence of a control group or a clear prospective rationale for choosing these therapies, it's hard for me to get too excited, particularly given that we don't know the denominator; in other words, we don't know how many patients with TNBC Burzynski has treated with this regimen who didn't respond. We also don't know the survival rates for these patients, only response rates.

It turns out that perhaps the best description of what "personalized" treatment means in Dr. Burzynski's hands comes from the Texas Medical Board's complaint against him, which can be found in over at the Ministry of Truth or at Casewatch. This complaint is based on the cases of two patients. First, here's Patient A, who is described in the complaint thusly:

1. Patient A:

a. In approximately May of 2008, Patient A presented to Respondent with breast cancer that had metastasized to her brain, lung, and liver.

b. Respondent prescribed a combination of five immunotherapy agents - phenylbutyrate, erlotinib, dasatinib, vorinostat, and sorafenib-which are not approved by the Food and Drug Administration ("FDA") for the treatment of breast cancer, and which do not meet the FDA's regulations for the use of off-label drugs in breast cancer therapy.

c. In combination with the five immunotherapy agents, Patient A was prescribed capecitabine, a chemotherapy agent. The concurrent prescription of five immunotherapy agents in combination with a chemotherapy agent resulted in Patient A suffering unwarranted side effects.

d. Respondent owned the clinic pharmacy from which the multiple drugs were ordered. Respondent failed to affirmatively disclose to Patient A his ownership interest in the pharmacy.

This is what's known as "throwing everything but the kitchen sink" at the tumor without any thought of interactions, as most of these agents have no proven role in the treatment of breast cancer. For example, erlotinib (brand name: Tarceva) is used to treat pancreatic cancer and non-small cell lung cancer. It works by inhibiting the tyrosine kinase of the epidermal growth factor receptor (EGFR) and is not FDA-approved for breast cancer. However, it's not unreasonable to think that it could work in breast cancer, as EGFR is believed to be important in some breast cancers, which is why this is an area of active research. Dasatinib (trade name: Sprycel) is also a kinase inhibitor. It inhibits the Src family tyrosine kinase. Vorinostat is a histone deacetylase inhibitor approved for use against cutaneous T-cell lymphoma. Finally, Sorafenib is another tyrosine kinase inhibitor that inhibits the tyrosine kinases of different receptors, as well as raf kinases. The big problem with this sort of approach is that the more drugs you add, no matter how "targeted" they are, the more chance for interactions that increase toxicity, and throwing all these kinase inhibitors together in a cocktail with chemotherapy is a recipe for disaster, particularly because such cocktails haven't been tested in proper phase I clinical trials to evaluate toxicity. They're also all incredibly expensive as well, and Dr. Burzynski sells them through his own pharmacy.

Patient B appears to be the patient with esthesioneuroblastoma whose case report I described above. This is the relevant passage from the complaint:

Follow-up magnetic resonance imaging ("MRI") scans were conducted in approximately August and December of 2003, and March of 2004, which showed progressive disease. Patient B was continued on phenylbutyrate during this 11 -month time period, and was not sufficiently informed about the drug's lack of efficacy on her disease.

The cost

It's very telling to look at the literature that Dr. Burzynski sends to prospective patients, one example of which is reproduced by Xeno. For example, rather than summarizing sound papers describing well-designed clinical trials, Dr. Burzynski only lists "response rates." Looking at the table included in the literature, I noticed immediately that Dr. Burzynski says nothing about survival rates, only what he calls "objective response rates," which are not defined in a meaningful way. The pamphlet defines them as as anything from an "improvement" (defined as "decrease in size of the tumors, not confirmed yet by the second follow-up radiological measurement") to "complete disappearance of all signs of cancer," which is utter bollocks. There are standardized ways of measuring tumor response agreed upon by radiologists and oncologists, such as the RECIST criteria. Burzynski lumps all responses together in an oncologically meaningless way. Also remember, Burzynski often uses standard-of-care chemotherapy along with his antineoplastons; so we would expect some responses. The chart above, however, is virtually meaningless, if only for the simple reason that initial tumor response often doesn't correlate to overall survival, and overall survival is what we care about. As Xeno also notes, the out-of-pocket costs are staggering. Contrast this to the clinical trials I mentioned above, where patients do not pay for the genomic profiling or chemotherapy.

As bad, Dr. Burzynski massively oversells what he is doing to desperate patients, and, if what he tells patients is the same as what he told Suzanne Somers in her book, appears to be misrepresenting what he does:

SS: When you talk about gene-targeted therapy, is that chemotherapy?

SB: No, this is not chemotherapy. Most of my patients have already had chemotherapy and it has not been effective for them. The beauty of antineoplastons is that they are natural compounds. They exist in our blood and form a protective system against cancer. You don't expect to have toxic side effects from chemicals which are normal in your blood. And they cover a broad spectrum of genes, which means from the very beginning we have a much better chance to help this patient.

Cytotoxic chemotherapy "covers" an even broader spectrum of genes; so by Dr. Burzynski's criteria, cytotoxic chemotherapy ought to be the best therapy of all! In any case, as we have seen, Dr. Burzynski does give chemotherapy. Lots of chemotherapy. He combines that chemotherapy with a gmish of "targeted therapies" based on a commercially available but not FDA-approved gene expression profile test and calls it "personalized gene-targeted therapy." Unfortunately, in my not-so-humble opinion, he doesn't have a scientifically supportable rationale for combining his targeted therapies. Instead, skirting the line between science and pseudoscience, Dr. Burzynski gives every appearance of recklessly throwing together untested combinations of targeted agents willy-nilly to see if any of them stick but without having a systematic plan to determine when or if he has successfully matched therapy to genetic abnormality.

One has only to compare what Dr. Burzynski does to what the group the University of Michigan, among other large research institutions, are doing to see that. The result is that his outcomes are basically uninterpretable, making them useless for determining whether his approach works. At the same time, the cost is personal in terms of giving patients false hope and unneeded side effects for little or no benefit and financial in terms of bills that run from tens to hundreds of thousands of dollars charged to patients who are so desperate that they will pay them for even a glimmer of hope.

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Note: Orac is away somewhere warm recharging his Tarial cells for further science and skepticism. In the meantime, he is rerunning some of his favorite posts. Given that the blog seems to have been infiltrated with Burzynski trolls again and Eric Merola threatens to make a sequel to the execrable…

A key pillar of the Stanislaw Burzynski antineoplaston marketing machine, a component of the marketing strategy without which his clinic would not be able to attract nearly as many desperate cancer patients to Houston for either his antineoplaston therapy (now under a temporary shutdown by the FDA…

Over the last couple of weeks, I've been spending a lot of time (and, characteristically, verbiage) analyzing the phenomenon known as Dr. Stanislaw Burzynski, his "cancer cure" known as antineoplastons, and his incompetent version of "personalized gene-targeted cancer therapy." In this third and…

It occurs to me that it's been a while since I've written anything about Dr. Stanislaw Burzynski. Truth be told, I had been hoping not to write about him for a while, and I had been actually succeeding. The last time I took notice of him was about a month ago, when his propagandist Eric Merola…

All of this just sounds like a scam wrapped up in enough actual "conventional medical treatments" and under the cover of "medical trials" to stay one step ahead of an FDA shutdown and an investigation for fraud.

If Burzynski's treatments were so "revolutionary," not only would the cancer community in general be demanding expanded trials by multiple research groups, but researchers themselves would be falling all over themselves to both prove and expand upon the success (which happens in just about every other research community).

Of course, if Burzynski opened up his books & actually published - he'd lose control over the massive revenue stream that he's created. And he keeps everything just secret enough, so that even though his patients keep dying, not enough of them know about the others to actually get a sense of how much of a failure he actually is.

It works just like a classic ponzi scheme - he is able to leverage the stories of those people who improve (again, most likely that small group of people with Cancer who improve on their own) to sucker in new clients, and again, ignore those that don't improve, but make more videos with the small slice that do.

By ignoring the negative results, he is able to make himself look like a miracle worker - because unlike real researchers and doctors that put both the good and bad on display in journal submissions, he only lists the positives.

Medicine in general gets maligned because it admits failure (which is also true of science in general) - that because it does not offer 100% solutions, whatever alt-med or science has to be correct (a giant straw man argument, but one with legs).

It is a travesty that this individual is continuing to con a very vulnerable community, that should be basing their decisions on the best possible range of options & not a suger-coated "miracle" cure.

What gene therapy is unable to overcome is the fact that the cancer cells become immune to the therapy after a short period of time. Medical treatment can only take the patient so far. What the cancer patient needs to recognize is that the enemy seeking to destroy their body is more than just a collection of cells. "Know your enemy" certainly applies here. Check out The Cancer Cure Experiment (www.thecancercureexperiment.com) for more information.

I get the impression this is less scam and more "mild" sophomoric quackery. Â With a dash of cargo-cult science.

Burzynski is using real chemotherapy (with one exception), with real treatment philosophies, to treat real cancers; he just seems to only partially understand how to do that. He thinks he has a level of resolution for precise targeting that doesn't exist, and appears to have mistaken or unfounded beliefs about the actions of some chemotherapy drugs.

It all smacks of an educated professional who's become pathologically overconfident in their own ability to recognize patterns and solve problems. Â His research is similarly tainted (you don't REALLY need controls or large samples or survival rates), and when even that fails to support him (as with antineoplastons), it's easy to distract himself from the problem. Â What REALLY matters is getting these vital drugs to patients by any means necessary, so if this research thing turns out to be harder than he thought, Burzynski can still exploit it to deliver the drugs he KNOWS work.

Of course, I could be totally wrong. Â I wonder about the length of time involved...after all this time, wouldn't he start to wonder? Â But I get the image of a guy who knows there's a scientific method out there somewhere, and honestly thinks that's a good idea, but sees it more as a set of...guidelines rather than rules.

What's up with all these companies offering tests of questionable value and validity? We've seen it with autism and mercury/heavy metals, with the WPI, with this Claris test, and I know I've heard of other examples. It seems like the philosophy is "we just sell it, we can't control what someone does with it", when these things are often clearly crafted to support or enable pseudoscience and quackery. Much like pharmacies selling homeopathy, I'm beginning to think this kind of irresponsible commercialism is a problem needing more attention.

Dr Orac's summary of Caris is itself dated. I called Caris and asked. They said they didn't really use the frozen samples anymore and said they preferred fixed samples.

all incredibly expensive ....sells them through his own pharmacy... Dr. Burzynski massively oversells what he is doing
Sounds like Burzynski is becoming an old fashioned oncologist, after all.

The basic problem here is that Burzynski's patients often have essentially been told to "F- off and Die," to quote a non-Burzynski discussion that I saw this week. They are not willing to call it a day and go home, or to hospice.

It might be more productive to create better avenues, for early adopters and the plain desparate. For example, say open treatment registries and interactive support groups for speculative treatments to bypass quackish data hoarders.

Unfortunately most of Dr B's audience isn't equipped to figure out his MO: it *sounds* like general information about genetic susceptibility to cancer, genetic testing, and differential response to therapies. Like the woo-meisters I survey he plays a spiel mimicking SBM that leaves out a great deal of information. And much to be desired.

Here is a relatively minor problem I encountered 5 years ago: I had a cold then developed an eye infection. I went to a doctor I knew personally: he first gave me eye drops and asked me to call in a few days. I still had the problem so he prescribed oral antibiotics and steroid-based eye drops. I had to call again, reporting that I was still not improving. He changed the meds again. This continued until I was entirely well after about 4 weeks. Whew! The doctor had a plan of action that was based on research- along the way, he informed me about what he was doing. I wonder what an ND would have done? I shudder to think about it.

Burzynski's method is not guided by research but he is addressing very serious illnesses.

Thank you very much for your continued "Rant"! Every time you open your mouth his stock seems to go up and that makes me very happy! FYI - he cured my father of Stage 3 Cancer of the pancreas! Quack? I don't think so!

On the surface, his basic claims sound very similar to the care and treatment my mother received for her breast cancer. She received/ is receiving a personalized treatment plan based on the type of cancer she has. The description of how they were treating her was very similar to some of what I've read above. However, there are two basic difference when you get down into the details.

1) The oncologist gave her a package of information on each of the medications used that included the results from large scale trials that support the treatment for her specific kinf of cancer, and with statistics on how effective they are. The package for Herceptin was excellent, and should be used as a sample for all publications like this.

2) Because all of her treatments are FDA approved, Medicare and her private insurance covered all but $1000 of her treatments.

Now that I think about it, in addition to bilking sick people, providing false hope, and providing suboptimal care; this quack is also making it impossible for his patients to provide informed consent for the treatments he is providing.

FYI - he cured my father of Stage 3 Cancer of the pancreas! Quack? I don't think so!

Okay, I'm interested. Stage III adenocarcinoma of the pancreas is normally considered unresectable and incurable.Just a few questions though:
- How was this tumor diagnosed - biopsy, resection or on imaging?
- How long has he survived since his treatment?
- How was he judged to be "cured"?
- Is his case presented in a peer-reviewed journal?

In short, this is an extraordinary claim, and as such, required good evidence to be considered valid. This includes a tissue diagnosis, and adequate followup to verify a cure. Independent evaluation of his case would be essential. If these requirements are met, this is such an unusual result that it would deserve a case report on its own. Dr. Burzynski is obligated, for the sake of people now dealing with cancer, to publish his results if they are so good. Why hasn't he?

That's because for Christians, cancer is simply a trial sent by god to test their faith. For the rest of us, it's a punishment for not being Christian. "Heads, I win; tails, you lose" is a very common attitude when religion comes into play.

In fact, I think I now prefer another term, which has been used by Cancer Research U.K., namely "stratified medicine." The reason is that what we as clinicians are doing when we "personalize" or "individualize" therapies isn't really "personalizing" the therapy so much as using various measurements and biomarkers to place patients into groups of patients who respond to specific therapies. What the modern version of "personalized" therapy is really doing is producing more and more groups of patients, each of which, is smaller than the last, to be matched to more and more therapies. Whether the groups will eventually reach an N of 1, I don't know, but that is the goal. Only then will we truly have "personalized medicine."

I was going to quibble with your dislike of "personalized" therapy, but I now see what you mean. If the terms "targeted" or "personalized" are being co-opted by quacks, then using another term, such as "stratified", is probably best.

If that will avoid confusion with the general public though, I don't know. It is easy to intuitively grasp what "personalized/targeted" means (even if it really is just throwing the kitchen sink at it when used by Dr. B), but the general public won't know what "stratified" means. Perhaps there is another term besides "stratified" that can be used, one that the public will understand--maybe stick with "targeted therapy" providing it truly is targeted???????

If he could do this for real, Burzynski could easily publish in high impact journals like Clinical Cancer Research, the Journal of Clinical Oncology, or another high impact clinical cancer journal. Heck, a result like that could probably make it into general medical journals, such as the New England Journal of Medicine or The Lancet, which have an even higher impact factor.

Agreed. It would probably also get into Science or Nature if he wished to put it into a more general high impact journal (Nature might even do a write-up anyway even if it appeared in The Lancet). I've read a few articles in Nature this past year regarding promising results/research looking for markers of specific conditions, diseases, cancers.
-dan

It all smacks of an educated professional who's become pathologically overconfident in their own ability to recognize patterns and solve problems.

Yet he evidently accepts that antineoplastons are not as good as the chemotherapy / immunotherapy drugs which now comprise the bulk of his practice. In other words, by his own lights he has spent several decades taking money from people for chemicals that aren't a silver bullet after all. How can he maintain *any* confidence in his ability?

"I checked your website out. I guess some of us are out of luck - atheists, agnostics, Hindus, Moslems, Buddhists, Jews, Unitarians and Wiccans for example."

I guess it is a stretch for some to believe that Jesus healed the sick and raised the dead--and still does. Being a "Christian" was not a prerequisite--neither was being a Jew--but having faith in Him was--and still is.

"That's because for Christians, cancer is simply a trial sent by god to test their faith. For the rest of us, it's a punishment for not being Christian. "Heads, I win; tails, you lose" is a very common attitude when religion comes into play."

Actually you have it wrong. It is "the god of this world"--Satan--who comes to "steal, kill and destroy"--not the God of the Bible. Jesus said He came that we might "have life." We all are victims of the destructive power of the god of this world--even Jesus died on the cross and Satan thought he had won the final victory--but the power of God was shown to be strong enough to overcome. Paul said "We battle not against flesh and blood, but against principalities and powers..." Those who turn to God find not just One where they will be kept in "the shadow of His wings," but a great and mighty warrior Who will fight both for and with them. Hence, The Cancer Cure Experiment: Are you willing to see if what God promises is true?

It is "the god of this world"--Satan--who comes to "steal, kill and destroy"--not the God of the Bible.

So to be clear, the same God who afflicted Job with boils and caused his tongue to cleave to the roof of his mouth so that he couldn't say "frankincense" without getting big laughs, and who created all living things down to the mosquito and HIV is above causing cancer or allowing it be caused?
And do you have any good evidence of the benefit of prayer in cancer cure rates?

Let me see if I've got this right - God will save someone from cancer, but only if they pray for it? God is omnipotent, omniscient (and so knows if they have cancer) and yet is so petty that he won't save someone unless they get down on their knees and pray?

I don't have anywhere near that kind of power, but I would save my children from cancer even if they spit in my face. In fact, I'd give my life to save my children and I wouldn't ask them to pray to me or even ask nicely.

Apparently, God doesn't love his "children" enough to do what is within his power to save them - not unless they worship him.

This recalls what a devoutly faithful acquaintance said after my child was diagnosed with autism. She said to me, "You know, God wouldn't have given you this burden if you couldn't handle it." To which I replied, "Do you mean that if I had been less capable, my child wouldn't be disabled?"

Clearly, in matters of faith, it is best to not think too much about the implications of what is said.

@ "Dr." Richard Moulton: I don't recall...did someone on this blog contact you for a consultation? What is your opinion of targeted therapies for cancer based on gene testing ordered by and interpreted by Dr. Burzynski...and antineoplaston cancer treatment?

Thanks for all the comments...I am interested in what is being said. I certainly understand the skepticism. I am not claiming that I have all the answers; that's why it's The Cancer Cure Experiment, not The Cancer Cure. None of us can control God's actions. But, let's face it, as much as medical science can help us, it still falls very short in addressing the destruction that cancer causes. If you've done any research at all on cancer, you can see the intricate defense mechanisms built into our bodies to prevent cancer from forming. However, cancer doesn't just "randomly happen" once in a million people. It happens all the time, and in the same ways. Rather anti-evolutionary, don't you think? Now, don't get me wrong. I have no problem with using the best that medical science has to offer. I think medical science is one of God's gifts to us. But I don't think it posits the whole answer of what is going on. Jeanne Achterber in Images of Cancer asked cancer patients to draw pictures of 1) what they thought their cancer looked like, 2) what their medical treatment looked like in relation to the cancer, and 3) what it looked like their bodies were doing to fight the cancer. She found she could predict with over 90% accuracy within a few months how long a cancer patient would live based on the pictures they drew. The "picture in our head" may very well influence the will and ability of our bodies to fight. The Bible offers great pictures of fights overcoming enemies. Real enemies. Physical enemies. Overcome. There is no reason we cannot win physical battles today in the same ways. Can we "make it happen"? No. Can we "try to make it happen"? Certainly. Can we live with faith-filled expectation for it to happen? Yes. Should we? That's a question you can only answer for yourself. I say, "by all means." You may say otherwise. That's okay. I'm only offering an approach for those who want to "experiment" with faith plus medicine...I continue to entertain your comments.

P.S. I have never claimed to be a medical doctor, and my web site makes that very clear. I am not intending to mislead anyone. In fact, my desire is only to offer something to those who are willing to grab hold. I am not charging any money for anything. I get no worldly benefits from doing this. I believe there is something we are missing that could hold a promise for more cures.

I guess it is a stretch for some to believe that Jesus healed the sick and raised the dead--and still does. Being a "Christian" was not a prerequisite--neither was being a Jew--but having faith in Him was--and still is.

Until unrelated researcher can replicate his results, I'll remain sceptical.

It would also help if his treatment was published in peer-reviewed journal. Preferably more recently than two thousand years ago.

The what's the point of your "experiment." If you get a lucky anecdote out of it, then you will likely claim that this "cure" works, if not, then you'll just accept as some greater wisdom that your god has a plan when he sends good people to a painful and slow death.

"I have never claimed to be a medical doctor, and my web site makes that very clear. I am not intending to mislead anyone. "

You know, I have an advanced degree as well. A doctorate in fact, of sorts, but it will be a colossal ass if I start prefacing my name with Dr. while discussing my latest "medical research." Somehow finding a magic cure turns every dentist and English post-doc into a wise doctor.

It also offers plenty of gruesome imagery of the almighty god overcoming all sorts of physical enemies, like Egyptian firstborn, cities of promiscuous people, disobedient early humans, the guy to torture on a dare from Satan, etc. Perhaps "real enemies" from a bible are often not real or not enemies?

However, cancer doesn't just "randomly happen" once in a million people. It happens all the time, and in the same ways. Rather anti-evolutionary, don't you think?

"anti-evolutionary"?
*facepalm*

What's anti-evolutionary about having cancer? As long as it doesn't stop the species from having children and survive...
Once again: evolution/natural selection does not work by making us healthy and living forever.
The only thing natural selection selects for, is the ability to have children who, in turn, will grow into adulthood and have children themselves.

Jeanne Achterber in Images of Cancer asked cancer patients to draw pictures of 1) what they thought their cancer looked like, 2) what their medical treatment looked like in relation to the cancer, and 3) what it looked like their bodies were doing to fight the cancer. She found she could predict with over 90% accuracy within a few months how long a cancer patient would live based on the pictures they drew.

Given that the patients are not total morons, why would this be surprising? The patients knew what their prognosis was; why, then, is it surprising that their illustrations reflected that? All that study did was show that the patients being studied had been given reasonably accurate prognoses by their doctors.

P.S. I have never claimed to be a medical doctor, and my web site makes that very clear. I am not intending to mislead anyone.

Just a tip, in case you're sincere -- coming to a medical blog, suggesting people visit a site about a cancer experiment, and signing your name "Dr So-and-so" will tend to lead people to the conclusion that you are a medical doctor. It's true you never overtly claimed to be an MD, and it's possible that you did not intend to mislead. However, you *did* mislead, and you would be wise to learn from that mistake so that it is not repeated. Assuming you are sincere, of course.

The above was intended for Richard Moulton. I'm continuing now with a longer post; I wanted to separate it as this is from one Christian to another:

I guess it is a stretch for some to believe that Jesus healed the sick and raised the dead--and still does. Being a "Christian" was not a prerequisite--neither was being a Jew--but having faith in Him was--and still is.

Having faith in Christ is a prerequisite but being a Christian is not? That's an odd thing to say, since the only universal requirement for Christian fellowship is accepting Jesus Christ as our lord and savior. How can you have faith and *not* be a Christian? Now, one might have faith in Christ but not call oneself a Christian, though I think you'd be hard-pressed to find any examples; the converse is certainly true, that one can call oneself a Christian yet have no faith in Christ.

For instance, there are many Christians who do not have faith in Jesus' gift of redemption. They do not believe it could possibly be what He said it was, and think that sinners cannot be saved. They spend more effort trying to keep people from finding about their iniquities than they do in tending to the sick or feeding the hungry or visiting the imprisoned; at some level, they do not trust Christ's redemption and don't want anyone else to notice. They also think that redemption isn't something given; it's something earned, and we all have the ability to earn it. As if God isn't more powerful than us, as if healing and atonement are up to us, not God.

But Jesus made it quite clear what should really be transparently obvious to anyone -- we cannot earn redemption. We are not God. That is our main mistake -- we think we can be perfect, and that only perfect people deserve salvation. The former is our natural hubris. The latter is our natural lack of faith. We tend not to believe that bad people could be forgiven.

And we start to think of Jesus and God as a sort of grown-up version of Santa Claus. Stay off the naughty list, pay back your sins, and maybe he'll give you something on your Christmas list. But it doesn't work like that. We want God to be giving us presents, but He made the world the way it did for a reason. I'm not saying cancer is a good thing; it's not. But it's not an accident that we are imperfect. Our imperfection is because creation isn't finished, and the strife we must endure is because strife is how it progresses. People think "strife builds character" or "good will come of ill", but these aren't actually accurate. These are human attempts to understand, but we will never completely understand. Why?

The story off Adam and Eve is, I believe, a parable. Possibly the most important parable of all -- we only get in trouble with God when we set ourselves as judges, and then we judge ourselves wanting and reject God. We believe we have the perfect ability to judge right from wrong. We do it all the time. We have to; it's part of our social makeup. But we apply it to everything, believing it to be universal rather than a social convention, and that's where we go wrong. We have the audacity to judge everything as right or wrong. We don't like cancer; therefore, it is wrong, it is evil, it must be defeated. But it isn't evil. Neither is it good. Like everything in nature, it is actually *neutral*. So asking why God sends evil upon the world in the form of cancer is the wrong question. Cancer is a natural process. It's unpleasant, and any sane person would want it not to happen to them and want it removed if possible. Why, then, does it exist? Because of evolution, and because of the way life arose.

Evolution is a fantastically elegant way of creating a magnificent diversity of life, don't you think? Yes, it hurts. Just as I'm sure it hurt Jesus to carry and then be nailed to that cross. We all have our crosses to bear if we want life to grow. It's not as simple as "cancer = bad, God = good, therefore God should be able to take cancer away from me if I ask nicely."

And what does God want us to do? Follow Jesus. He doesn't mean go to the right church, say the right prayers, take Communion in the right way. He means do what Jesus did. Walk in His footsteps. Let Him lead you. You don't have to call Him by name, you don't have to call yourself a Christian, you don't have to believe in an afterlife. (In fact, I think someone who does this only for a heavenly reward is doing it for the wrong reason.) It means love your neighbor as yourself. It means serve one another, just as Jesus did.

Not a lot of Christians do this. It's hard. It's very hard. I'm bad at it myself. This is because I am human. But we do need to try, and keep trying.

God won't take your cancer away because you pray for it. But He will be with you. He's always been with you. You can take comfort from that, and personally, I find prayer very helpful for that. But cancer is part of the world, and you are part of the world. God does not send us trials to test us; He already knows us. There is not a hidden meaning in these things. But by striving through hardship, we as a people do become stronger. If everything was available by magic or by prayer, we would never progress, and where would be the point in creation then?

I do not believe in intelligent design; I think the proposition is insulting to God, honestly. Evolution is arbitrary. But arbitrary is not the same thing as pointless, and I've never understood why some believers have a problem with that.

Hey everyone, join with me in trying the 'Cancer Quack Cure Experiment.' You don't have to believe in Jesus. You just have to pray that "Dr." Moulton will jump in a lake. If I really had the power to make him jump in a lake, it would be the Cancer Quack Cure.

If this is an experiment, what steps are you taking to ensure high-quality data? How, in other words, are you protecting against self-deception and misinterpretation?

What blinding procedures are you using?
How big is your sample?
How is your sample selected?
What objective measures are you using to determine degree or type of faith?
What objective measures are you using to determine outcome?
What predictions are you making based on potential outcomes; that is, what will positive or negative results tell us?
What statistical methods will you be using to analyze your results?
Who is providing oversight and review, given that this is human experimentation?
Who is funding the research?

There are plenty of other questions to consider in a project like this, but those are the main ones I'd like to hear answers to.

Mr. Moulton, thanks for derailing what was a thread about a real issue in cancer care. I'm sure we're all much happier veering off into crazyland with you where we can debate about the reality of your imaginary sky-fairy, especially since it's so much more fun than contemplating a daunting and very complex problem going on down in Texas. Is Dr. Burzynski a charlatan? Is he deluded? Is he a conman? Is he on to something? These are all valid questions. Yes, your wishful thinking experiment based entirely on the existence of a mercurial, sociopathic, supernatural being (one of thousands our species has hatched) is not helpful because it is not based on reality (at least antineoplastons actually exist). Thanks for your good intentions, unctuous sincerity and magical-thinking. Run along and show your felt-board bible experiment to your friends, the grown-ups are talking.

Looks like somebody is plagiarizing your posts. And not doing a particularly convincing job of it either: Link (nofollowed to deny them pagerank). Dumb schmuck left the trackback code in your link to White Coat Underground when they copypastaed it.

This year, I beat stage 4B non-Hodgkin's lymphoma. I am still an avowed atheist.

I don't buy for a second that "Satan" is responsible for ill and evil in the world. Either your god is omnipotent, OR he's locked in an eternal struggle with the Devil. You can't have it both ways.

It is extremely dishonest to call yourself "Dr. Moulton", opine about cancer and recovery and direct people to your website devoted to cancer, then say, "But it's okay! I never claimed to be a medical doctor!" Go to hell. Furthermore, I spit on your "D.Min.". I can't think of a more useless degree and a more useless field than theology. Mental masturbation, the lot of it.

I guess it is a stretch for some to believe that Jesus healed the sick and raised the dead--and still does.

YES. It is. Have you never heard the phrase "Extraordinary claims require extraordinary evidence," or do you just not grasp it?

Being a "Christian" was not a prerequisite--neither was being a Jew--but having faith in Him was--and still is.

Don't you see the contradiction here? "You don't have to be a Christian or a Jew, you just have to believe in the biblical God". Or, if the "Him" you refer to is Jesus, it's even worse. "You don't have to be a Christian, you just have to believe in Jesus Christ." Words have meanings - you can't just hand-wave away their definitions to make them mean whatever you want.

"You don't have to be a Christian, you just have to believe in Jesus Christ."
I had assumed that Dr Moulton's use of scare quotes around "Christian" in comment #29 was to distinguish between those who are religious in name only and those who truly have faith. The difference is presumably that prayer only works for the latter. If it doesn't work, obviously you weren't a real christian anyway.

I'm very confused by all of the rambling done on here. It seems that all of the people on here have to shout in order for their opinions to matter, but of course, this is not the place to play with fire. I suggest everyone to move on over to a well adjusted site for this. May I suggest www.reddit.com, I have enjoyed posting thIngs there and up/down voting other's posts and comments. It's far from perfect and may be subject to some web bots, but it does the job.

Scientific process is not determined by "popularity," in the same way, scientific evidence isn't either.

To address this particular topic, cancer treatments are not determined by popularity, but by effectiveness - and in this case, after 30 years, this is not an effective treatment, so your opinion doesn't mean squat without proof.

I'm very confused by all of the rambling done on here. It seems that all of the people on here have to shout in order for their opinions to matter, but of course, this is not the place to play with fire. I suggest everyone to move on over to a well adjusted site for this.

It's not that bad. We have a couple of resident trolls, but nothing that you can't fix with some killfile and five mouse clicks.

Personally I like style and feel of this blog and of most of the posters. In the long term the discussion boils down to facts vs. feelings, but at the end of the day science wins and insolence is delivered as it should be. If you have facts, you don't have to shout.

Facts vs feelings! I love it!
One of the problems in combatting woo and those who spread it to the masses is the time element: it takes time to give the details of complex subject matter like that which is discussed @ RI. Feelings are immediate,they affect how well material is remembered, and their expansive aura may cloud judgments based on facts. Which is why woo-meisters like getting people all whipped up into a frenzy or too frightened to think straight. Their arsenal includes shouting, shrieking, and obviously, bending the facts to suit their own designs. To make matters even worse, people become accustomed to this style.

So how can their most reliable incendiary devices be de-fused? We can reveal how this works: if you read something at NaturalNews or AoA, you'll see how the language aims at emotional reactions first and foremost while opinion is presented as fact. Then look at an encyclopaedia or a standard text on a similar subject. Notice the cleaner, informative language. Also talking about the propagandist's motivations often casts a light on the inner workings of their method. They're not doing this for free or anonymously.

I certainly do not want to support Burzynski, but it makes me wonder if there are other not-so-bad docs doing similar off-label treatments to patients, and if it's about the money, or if they think they are helping. Warning: I am only familiar with first-line therapy research pretty much.

The year-ago Van Hoff paper (PMID: 20921468) also used testing from Caris, and did off-label treatments. What is there to stop an ordinary doc from doing the same for their patients? In their trial, of the 66 patients that mattered most, 35 had 2-4 previous therapies, 25 had experienced 5-13. I was shocked, perhaps just naive. I vaguely know that for some cancers you fight it in many rounds. Maybe many of those were clinical trials, and that might explain part of it too. I feared someone was willing to keep on trying the next thing forever though - hope I'm wrong.

To restate: if I tone down the salesmanship and use of non-approved drugs, and clean up a few other odds and ends, why can't I just keep trying the next plausible FDA approved drug off-label for my patients, as a way to make a living? I might even prolong a life on occasion. Insurance won't pay? It's OK, I only need a certain number of rich or desperate people who will be dead very soon anyway to pay out of pocket. I think that general question more interesting than the specifics of how this one guy is doing it wrong. Not that he should be spared.

PS for readers of Hoff: The Hoff paper gets 27% of their patients to have the ratio of progression-free survival (PFS) in the current treatment to the previous treatment be greater than 1.3. They demonstrate that is better than 15% for some reason I can't figure out (if you can, tell me). I simulated the current PFS as an exponential distribution with mean 2, and the previous PFS as exponential with mean 4, and that they are independent (not realistic), so that the current treatment is twice as bad as the last one on average. I get the PFS ratio to be greater than 1.3 about 27% of the time anyway (1000 simulated patients), thanks to the wonders of random variation. Just a sweet coincidence that it agreed with their 27%. So killing people twice as fast on average gets me a result that I helped lots of people, if I use their statistical methods. I thank the grave and learned reviewers who did not think these issues were worth hassling the authors about.

I heard about the threats on Burzynski's "behalf", but have only been reading up on it over the last day or so. The saga of Burzynski and antineoplastons reminds me of the H.G. Wells story "The Diamond Maker", which I have always appreciated as a parable of the practical problems of research and development. In that context, I have been struck by the fact that, at this late date, it might very well not MATTER if Dr. B can produce results. He has spent so many years reporting results that others could not reproduce as to be in potentially the same bind as "the boy who cried wolf". I find it particularly significant that, if one did not question his honesty in reporting results, one could raise almost more damaging questions about his objectivity and judgment.

By a strange coincidence I read this thread at around the same time I was reading a lung cancer discussion forum. My mother died from lung cancer so I am still reading it occasionally. One question asked there by someone seems to be exactly what Orac mentions here about some of those "integrative" doctors combining targeted drugs with other drugs.

Someone there went to an "integrative oncologist" who suggested talking to his main doctor about taking new targeted drug crizotinib with Avastin.

Now, I am no doctor, but I do know a little about crizotinib because my (late) mother was in clinical trials for it. It worked well for my mother - some reduction at first then stable - and with no side effects that she noticed, I don't know how long it'd have been working had her lungs not been in such bad shape to begin with from both cancer and failed pleurodesis (long story; anyway she died from either a blood clot or infection - she was on prednisone from before the trial as it helped her breath).

BUT.... Some things I do know about crizotinib is that 1) it only works for people with EML-ALK4 mutation 2) for people with this mutation, there is a very high response rate 3) I've never heard it's being tested in any combination 4) it comes in pill form and has minimal side effects.

One thing I definitely remember from the clinical trial was that my mother had a long list of things she was not supposed to be taken with it, and any kind of drug for anything had to be approved by the clinical study people.

Now, I am no doctor so I may be missing something here, but this whole idea didn't make any sense to me at all. Why not have the test first to see if the guy even has the mutation? If he does, why not try the drug that has been shown to work for this mutation alone given as this was how it was tested? Of course, I am just an ignorant layperson...

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